Discovering the origin of congenital mitral fistulas

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Scientists from the Department of Animal Biology at the University of Malaga have discovered the cellular mechanism that generates coronary arterioventricular fistulas, a congenital anomaly that, in severe cases, may lead to death.

José María Pérez Pomares, Professor at UMA, member of IBIMA-Plataforma BIONAND, conducted this study in collaboration with researchers from the National Center for Cardiovascular Research (CNIC) in Madrid, the Mother and Child Hospital in Malaga, and the Center. for Applied Medical Research (CIMA) in Pamplona, ​​and the Necker Hospital and Institut Pasteur/Imagine in Paris. The results have been published in the scientific journal Experimental and Molecular Medicinefrom the respected publishing company nature.

aberrant connections

Coronary fistulas are abnormal connections between various blood vessels in the coronary artery system, large arteries or veins (aorta, pulmonary, or vena cava) or other parts of the heart, such as its chambers (atria and ventricles). The most common type of coronary fistula is precisely this last one, the type that connects one of the coronary arteries to the inside of the heart, and it is the type of fistula studied by these researchers from the University of Malaga.

It is estimated that between 0.21 and 5.8 percent of the population has coronary artery anomalies, and between 0.1 and 0.2 percent of patients who undergo coronary artery bypass screening have a fistula. “It is a relatively low incidence, although we must bear in mind that in many cases, the presence of this defect is not diagnosed,” explains Perez Pomaris.

While fistulas are often small and do not involve serious conditions or complications, allowing sufferers to live a normal life, larger fistulas may be associated with serious complications, such as endocarditis — an infection of the tissues that cover the heart internally — or enlargement or dilation of the walls of the heart. ventricular or sudden death.

“The pathology is related to other heart diseases; the spectrum is highly variable,” says the UMA professor.

early diagnosis

This congenital malformation is known to appear during embryonic development, although so far there is limited information on its origin.

Therefore, Perez Pomaris, who chaired the Working Group on Development, Anatomy and Pathology of the European Society of Cardiology for two years (2018-2020), led one of the few studies explaining the causes of this defect, a study that may help improve early diagnosis of this type of anomaly. and other associated diseases.

The results indicate that the appearance of discontinuities in the ventricular wall lies at the origin of this mitral defect.

The UMA professor points out that the chambers of the heart have three layers of tissue: the endocardium, which is most of the inner tissue; myocardium, the thick central layer, which enables the contraction of the atria and ventricles, and thus the circulation of blood; The epicardium that covers the outer surface of the organ.

When the endocardium and epicardium come into contact abnormally during the early stages of embryonic development, usually because the myocardium separating these two layers have abnormally thinner regions or follicular regions, a contact is created between the surface and the interior of the heart, which causes the fistula to mature into a fistula.

In conducting this study, Perez-Baumares’ team worked with both genetic and experimental animal models, but they could also study human samples of a specific case of pediatric coronary fistula. These samples were obtained through informed consent for research purposes. The findings open the door to identify new candidate genes for early diagnosis of these birth defects and the risks associated with them.

source:

Journal reference:

Palmquist-Gomes, P., et al. (2023). The origin of congenital coronary arterioventricular fistulas from epicardial dysplasia and cardiomyopathy. Experimental and Molecular Medicine. doi.org/10.1038/s12276-022-00913-x.

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